Hepatitis C virus (HCV) is a global disease of the liver that affects over 170 million people. The only approved treatment for chronic hepatitis C is interferon (IFN) and ribavirin, which only cures about 50% of infected patients. Given the chance of success and significant side effects associated with IFN therapy, many patients consume botanicals such as milk thistle. The active ingredient in milk thistle is Silymarin (SM), which is thought to promote a healthy liver. However, exactly how SM promotes a healthy liver is not known. Furthermore, the botanical industry lacks proper standardization of the source plants and preparation of botanical extracts. We propose to determine how SM promotes a healthy liver, using a carefully standardized and validated preparation of SM. We hypothesize that SM acts as an anti-inflammatory and anti-viral agent to protect the liver from HCV infection. We believe these studies will provide a solid foundation for future clinical trials of SM in patients with chronic hepatitis C. Project Narrative: Chronic hepatitis C is a global disease of the liver that affects over 170 million people. It is caused by a hepatitis C virus (HCV). Treatment options for infected people are limited, expensive, associated with major side effects, and frequently of limited efficacy. This project will investigate the mechanisms of hepatoprotection of the botanical silymarin to provide a rational basis for alternative and complementary medicine approaches to treatment of chronic hepatitis C.